Electrospinning scaffolds composed of antibiotics and natural polymers can be helpful in the simultaneous suppression of infectious procedures and inducing tissue healing in the treatment of bone infections. The present study was performed to prepare and determine antimicrobial effects, biocompatibility, and osteogenic effects of gelatin meropenem/vancomycin -mesoporous silica nanoparticles (Mrp/Van-MSNPs) prepared using an electrospinning procedure. The scaffolds were investigated for physicochemical features, antimicrobial, biocompatibility, and osteogenic properties. The scaffolds showed applicable mechanical features, slow drug release patterns, and showed antimicrobial effects for 21 days. Gelatin-Mrp/Van-MSNPs showed higher antimicrobial and bacterial adhesive effects than gelatin and gelatin-Mrp/Van. All prepared scaffolds exhibited in vitro favorable biocompatibility. Gelatin-Mrp/Van-MSNPs significantly induced the MSCs' attachment, viability, and proliferation. It also significantly triggered the alkaline phosphatase (ALP) activity and induced the expression of osteogenic genes in both the early and late stages of differentiation. Therefore, the gelatin scaffolds with Mrp/Van-MSNPs can be considered for treating osteomyelitis. The addition of MSNPs and antimicrobial drugs in gelatin was not significantly associated with unfavorable effects on gelatin properties. The MSNPs led to improved antimicrobial, biocompatibility, and increasing cellular proliferation, and induced osteogenesis properties of gelatin.